Recognizing When 1L Treatment Isn’t Enough: Signs You May Need 2L Therapy
Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease that affects the bile ducts, leading to liver damage over time. For many patients, the journey begins with a first-line (1L) treatment—ursodeoxycholic acid (UDCA), which has long been the gold standard for managing the condition. However, for a significant number of patients, 1L therapy is not enough to adequately control the disease. If you’ve been on UDCA or another 1L therapy for PBC, it’s essential to recognize when it might be time to consider a second-line (2L) therapy, such as IQIRVO or other available options. Here’s what you need to know about recognizing the signs that your 1L treatment isn’t working and when it may be necessary to discuss 2L options with your doctor.
Understanding the Role of 1L Treatment
UDCA has been the cornerstone of PBC treatment for decades. It works by helping bile flow more easily through the liver, reducing liver damage. While UDCA can slow the progression of PBC in many patients, it’s not always enough. Up to 50% of PBC patients on UDCA remain inadequately controlled, meaning their liver function markers—such as alkaline phosphatase (ALP) levels—don’t improve to target ranges, or they continue to experience troubling symptoms.
If your disease isn’t responding to UDCA or another 1L treatment, it may be time to consider a switch or add-on therapy. Understanding the signs that indicate your current treatment isn’t effective is the first step toward taking control of your health and finding a more effective option.
Key Signs Your 1L Therapy May Not Be Enough
Persistent Elevated ALP Levels
Alkaline phosphatase (ALP) is an important marker for liver function in PBC patients. High ALP levels indicate that the bile ducts are still inflamed, meaning liver damage may be continuing despite treatment. Most patients on 1L treatment should see their ALP levels drop significantly within 6 to 12 months of starting therapy. If your ALP remains elevated or only shows minimal improvement, this may be a sign that your 1L treatment isn’t adequately controlling the disease.
Worsening Fatigue
Fatigue is one of the most common and debilitating symptoms of PBC, and it can have a major impact on quality of life. While UDCA may help reduce liver inflammation, it doesn’t always alleviate fatigue. If you find that your energy levels continue to decline or that fatigue is affecting your daily life, it could be a sign that your liver disease is not being controlled well enough by 1L treatment. This is a key indicator that a 2L therapy may be needed.
Persistent Itching (Pruritus)
Chronic itching, or pruritus, is another common symptom of PBC. In some cases, UDCA can reduce itching, but for many patients, it persists. If you’re still experiencing severe itching despite 1L treatment, it could be a signal that the bile acids causing the itch are not being effectively cleared from your liver and bloodstream. Discussing 2L treatment options with your doctor could provide relief.
Development of Cirrhosis
Cirrhosis is the advanced stage of liver damage, where scar tissue replaces healthy liver tissue. If cirrhosis develops or progresses despite being on UDCA, this is a clear sign that 1L treatment is not sufficient to stop the disease’s progression. Early intervention with a 2L therapy may help slow or prevent further damage.
Liver Function Tests Are Not Improving
Regular liver function tests (LFTs), including ALP and bilirubin, are essential in monitoring your response to treatment. If these markers are not improving or are worsening, it indicates that liver inflammation and damage are continuing despite treatment. In this case, adding or switching to a 2L therapy could be necessary.
Symptoms of Portal Hypertension
Portal hypertension occurs when blood flow through the liver is restricted due to damage, causing pressure to build in the portal vein. Symptoms can include abdominal swelling (ascites), enlarged veins in the stomach or esophagus (varices), and confusion due to toxin buildup (hepatic encephalopathy). These symptoms suggest advanced liver disease and require a re-evaluation of your treatment plan, including consideration of 2L therapies.
Why 2L Therapy Can Make a Difference
Second-line therapies, such as IQIRVO, offer new mechanisms of action that can target PBC in ways that UDCA and other 1L treatments cannot. For example, IQIRVO is a dual PPAR (alpha and delta) agonist that addresses both bile acid regulation and inflammation, helping to reduce liver damage and improve symptoms in patients who are inadequately controlled on UDCA. For those with persistent symptoms or lab results indicating poor disease control, 2L therapies can offer new hope for better outcomes and improved quality of life.
When to Talk to Your Doctor About 2L Treatment
If you recognize any of the signs mentioned above, it’s time to have a conversation with your doctor about your treatment options. Prepare to discuss your current symptoms, lab results, and how PBC is affecting your life. By advocating for yourself, you can work with your healthcare team to determine whether switching to a 2L therapy like IQIRVO could help you achieve better disease control and improve your overall well-being.
Recognizing when 1L treatment isn’t enough is critical for managing PBC effectively. By staying proactive and informed, you can take steps toward finding a treatment plan that works for you.